Treatment of localized osteosarcoma with amputation alone has historically resulted in long-term relapse-free survival of approximately 20%, although recently relapse-free survival of greater than 40% has been reported in surgically-treated patients. Although several chemotherapeutic agents have been found to cause tumor stabilization or regression in patients with overt tumor, their benefit in the adjuvant setting following surgical removal of all identifiable tumor is much debated. The objective of this multi-institutional study is to evaluate the efficacy of adjuvant chemotherapy using the currently available front-line drugs in children with localized extremity osteosarcoma. Following either amputation or limb salvage procedure, patients are randomized to receive either a 43-week course of chemotherapy using bleomycin/actinomycin D/cyclophosphamide, high-dose methotrexate, adriamycin and cis-platinum (regimen 1), or no immediate chemotherapy (regimen 2). Patients being observed on regimen 2 will receive chemotherapy only in the event of overt tumor recurrence, following attempt at surgical resection of all recurrent tumor. Both time to first relapse and ultimate survival are being evaluated. Since May 1982, approximately 35 patients have been randomized on this study (16 from NCI) of whom 29 have been evaluated in the most recently available Pediatric Oncology Group report. Although there is at least a trend towards superiority of the chemotherapy arm in time to first relapse, detailed review is bieng performed before full statistical analysis is completed. There is at present no difference in ultimate survival between the two arms.